What question did this study set out to answer?

To evaluate whether ex vivo reprogramming of macrophages using HDAC6 inhibitors prevents tumor-induced phenotypic switching and enhances antitumor immunity in melanoma models.

September 14, 2024Journal of Experimental & Clinical Cancer ResearchOpen Access

Cell therapy using ex vivo reprogrammed macrophages enhances antitumor immune responses in melanoma

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To evaluate whether ex vivo reprogramming of macrophages using HDAC6 inhibitors prevents tumor-induced phenotypic switching and enhances antitumor immunity in melanoma models.
Treated murine bone marrow-derived macrophages ex vivo with HDAC6 inhibitors to modulate STAT3-mediated signaling pathways.
Administered reprogrammed macrophages intratumorally via adoptive cell therapy into syngeneic SM1 murine melanoma and NSG-SGM3 humanized patient-derived xenograft mouse models.
Assessed tumor infiltration, viability, and cellular phenotypes using flow cytometry, histological staining, bulk RNA sequencing, and single-cell RNA sequencing.
HDAC6 inhibition prevented STAT3-mediated M2 polarization, keeping transplanted macrophages viable and locked in an antitumor M1-like state two weeks post-treatment.
Intratumoral adoptive transfer of reprogrammed macrophages significantly diminished melanoma tumor burden across both syngeneic and humanized mouse models.
Single-cell and flow cytometric analyses revealed a significantly increased M1/M2 macrophage ratio alongside heightened infiltration and activation of CD8 effector T-cells and monocytes.

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Implication

Preclinical study demonstrates that adoptive therapy using HDAC6-inhibited macrophages halts tumor growth in melanoma models, highlighting a strategy to maintain antitumor macrophage polarization.

Cite This Study

Noonepalle et al. (2024) studied this question.

synapsesocial.com/papers/6a7df26a30df0be8fb5ca180 https://doi.org/10.1186/s13046-024-03182-w

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Implication

Preclinical study demonstrates that adoptive therapy using HDAC6-inhibited macrophages halts tumor growth in melanoma models, highlighting a strategy to maintain antitumor macrophage polarization.

Cell therapy using ex vivo reprogrammed macrophages enhances antitumor immune responses in melanoma

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Discussion

Implication

Cite This Study

Cell therapy using ex vivo reprogrammed macrophages enhances antitumor immune responses in melanoma

Key Points

Discussion

Implication

Cite This Study

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